As noted in U.S. Pat. No. 6,228,852B1,
“Progesterone is a steroid hormone that is produced by the ovaries during a woman's child-bearing years. Progesterone is also made, although in smaller amounts, by the adrenal glands in both sexes and by the testes in males. An astonishing variety of physiological functions are mediated by progesterone (See e.g., Lee, 1993, Natural Progesterone, BLL Publishing, Sebastopol, Calif.). For example, progesterone, which surges following ovulation, maintains the secretory endometrium and thus, helps to ensure the survival of the embryo and fetus. It also acts as a diuretic, an antidepressant, and as a precursor of corticosteroids and of other sex hormones, notably estrogen and testosterone. There is also evidence that progesterone affords protection against loss of libido, osteoporosis, endometrial cancer, breast cancer, and fibrotic cysts.”
As women age, they experience a decline in the production of progesterone, estrogens and androgens. In addition to uncomfortable symptoms, such as hot flashes, sleep disturbance, and cognitive challenges, which are frequently experienced at around the time of menopause, there is an increase in the prevalence of debilitating conditions, including heart disease, loss of skeletal muscle, osteoporosis, cognitive decline and the possibility of stroke.
At present, a common form of treatment for many of the above conditions is oral administration of estrogen. In addition to oral administration, estrogen may be introduced to the body by a vaginal suppository, intramuscular injection, buccal mucosa pouch and in sublingual troches, transdermal patch, creams and gels, nasal mucosal spray, and subcutaneous implant. In a similar manner to estrogen, other hormones such as progesterone, testosterone, and dehydroepiandrosterone (DHEA) may be administered as active pharmacological ingredients in support of a hormone replacement therapy regime. However, there is the possibility of substantial adverse systemic side effects arising from the misuse of any of these replacement hormones. These adverse effects include possible contributions to endometrial hyperplasia, adenocarcinoma, breast cancer, thrombophlebitis, pulmonary embolism, cerebral thrombosis, mental depression, nausea, insomnia, fluid retention, migraine headache, liver dysfunction, weight gain, acne and more.
In addition to systemic side effects, there are specific local side effects associated with the method of administration. U.S. Pat. No. 8,026,228 teaches oral administration of hormones, but due to gastrointestinal degradation of the drug and the “first pass effect” in the liver, oral administration of estrogens requires higher than medically necessary doses to obtain the proper therapeutic level in the body thus possibly elevating the probability of systematic side effects. U.S. Pat. No. 8,629,129 teaches the use of vaginal suppositories which can, if the woman is having intercourse, be transmitted to her partner. Suppositories can also cause irritation due to a high local drug concentration, and can have a tendency to dislodge and exit the vagina during activity. U. S. Publication. No. 2005/0282749 teaches administration via intramuscular injection, but such administration may require a visit to a medical facility, is inconvenient for frequent doses, and can cause site injection irritation due to a high local drug concentration. This method, as well as pellet injection, does not allow for minor dosage alterations based upon symptoms of insufficiency or excess varying with actual day to day needs. U.S. Pat. No. 7,951,398 teaches transdermal patches, which while popular, require the diffusion of drugs across a limited surface area that can cause irritation due to a high drug concentration, and furthermore, penetration enhancers, often used in transdermal patches, can also cause skin irritation. U.S. Pat. No. 6,117,446 teaches buccal administration to the mucosal membranes of the mouth, but such administration can lead to significant quantities of the hormones being swallowed, thus subject to the “first pass effect.” It can also lead to high drug concentration irritation like other methods. PCT Publication No. WO1998006404 teaches using a subcutaneous implant, but such administration requires a visit to a medical facility and does not lend itself well to monthly breaks or mini-variations in hormonal dosage needs as is common. Also, it is inconvenient for frequent doses, and furthermore, the implant site is subject to irritation due to a localized concentration of the drug. Additionally, if required, the removal of the implant may prove to be difficult. U. S. Publication No. 2006/0147385 teaches the use of nasal mucosal spray, but such application requires a high drug concentration due to the short application time, has a rapid absorption time thus producing excessive hormonal dosage peaks, and is likewise subject to induce local irritation. U. S. Publication No. 2004/0266688 teaches intravenous administration, but such administration requires excessively frequent visits to a medical facility, as well as also producing unphysiological hormonal dosage peaks, and is inconvenient for frequent doses.